The basis of this proposal seeks the to develop new reaction methods in synthetic organic chemistry, their application to biologically active complex natural products and investigations of fundamental importance in synthetic and medicinal chemistry. This includes efforts to develop new chemistry for the [4 + 2]-annulation of enantioenriched organosilanes. An extensive investigation seeking to evaluate functionalized organosilane reagents for the stereoselective construction of dihydropyrans and tetrahydropyridine ring systems with the eventual goal in their application in synthesis. The enantioselective synthesis of the cytotoxic agent callipeltoside A and the transcription activator of low density lipoprotein receptor will pursued with emphasis on the dihydropyran annulation chemistry. [unreadable] [unreadable] Novel annulation methodology for the stereoselective synthesis of nitrogen bearing heterocycles will be directed at the synthesis of alkaloid 205B. [unreadable] [unreadable] A convergent, enantioselective synthesis of the potent cytotoxic / antifungal agent, leucascandrolide A will be achieved and will suitable for the preparation of side chain analogs with widely diversified substitution patterns. A small focused library of heterocyclic sidechain analogs will be assembled and evaluated for their effectiveness in inhibiting Candida albicans. [unreadable] [unreadable]